Method and system for diagnosing and treating preeclampsia

Abstract

Described herein are methods, systems and kits of the diagnosis of preeclampsia and HELLP syndrome, as well as the selection of a preeclampsia or HELLP syndrome treatment. These are based, at least in part, on the finding that proximal tubule injury, as measured by urinary KIM-1, is increased in severe preeclampsia and correlates with complement activation. The detection of complement proteins correlate with kidney injury in severe preeclampsia and/or HELLP syndrome and terminal complement blockage is a therapeutic approach taken as described in various embodiments of the present invention.

1 . A method of diagnosing preeclampsia or HELLP syndrome and optionally administering a preeclampsia therapy or HELLP syndrome therapy, comprising:
 assaying a biological sample obtained from a subject to determine a level of a preeclampsia biomarker selected from the group consisting of kidney injury molecule 1 (KIM-1), a complement protein or component, and combinations thereof, wherein determining the level of the preeclampsia biomarker is by application of a reagent comprising a detectably labeled probe that reacts with the preeclampsia biomarker or a complex comprising the preeclampsia biomarker;   comparing the preeclampsia biomarker level to a reference level; and   diagnosing preeclampsia if the level of the preeclampsia biomarker is higher than the reference level.   
     
     
         2 .- 51 . (canceled) 
     
     
         52 . The method of  claim 1 , wherein the reagent is an antibody. 
     
     
         53 . The method of  claim 1 , further comprising administering the preeclampsia therapy or HELLP syndrome therapy to treat preeclampsia or HELLP syndrome if preeclampsia or HELLP syndrome is diagnosed. 
     
     
         54 . The method of  claim 1 , wherein the complement protein or component is C3a, C5a, C5b-9 or combinations thereof. 
     
     
         55 . The method of  claim 1 , wherein the complement protein or component is a complement protein or component upstream from KIM-1. 
     
     
         56 . The method of  claim 1 , wherein the complement protein or component is a complement protein or component downstream from KIM-1. 
     
     
         57 . The method of  claim 1 , wherein the biological sample is urine and the level of the preeclampsia biomarker is normalized to urine creatinine level. 
     
     
         58 . The method of  claim 1 , wherein the preeclampsia therapy or HELLP syndrome therapy comprises a complement protein inhibitor. 
     
     
         59 . The method of  claim 1 , wherein the preeclampsia therapy or HELLP syndrome therapy comprises Eculizumab. 
     
     
         60 . The method of  claim 1 , wherein the preeclampsia therapy or HELLP syndrome therapy comprises Pexelizumab. 
     
     
         61 . The method of  claim 1 , wherein the preeclampsia therapy or HELLP syndrome therapy comprises Compstatin. 
     
     
         62 . The method of  claim 1 , wherein the preeclampsia therapy or HELLP syndrome therapy comprises sCR1. 
     
     
         63 . The method of  claim 1 , wherein the preeclampsia therapy or HELLP syndrome therapy comprises Heparin. 
     
     
         64 . The method of  claim 1 , wherein the preeclampsia therapy or HELLP syndrome therapy comprises magnesium sulfate, an antihypertensive drug, or combinations thereof. 
     
     
         65 . The method of  claim 1 , wherein the preeclampsia therapy or HELLP syndrome therapy comprises hydralazine and labetalol, nifedipine, sodium nitroprusside or a combination thereof. 
     
     
         66 . The method of  claim 1 , further comprising:
 assaying the biological sample to determine the level of an additional preeclampsia biomarker selected from the group consisting of CD46, CD55, and CD59, PlGF, PP13, PAPP-A, Inhibin A, Activin A, MMP-9, Endothelin-1, P-selectin, NGAL, sEng, triglycerides, HDL cholesterol, LDL cholesterol, hPL, SP-1, hCG, sL-selectin, ApoB, TGF-β1, TNF-R1, TNF-R2, complement activation product Bb, triglycerides, PAI-2, IGFBP-1, free foetal DNA, sFlt-1, sEng, BNP, and combinations thereof; and   comparing the level of the additional preeclampsia biomarker to a reference level for the additional preeclampsia biomarker; and   wherein diagnosing preeclampsia or HELLP syndrome comprises diagnosing preeclampsia or HELLP syndrome if the level of the preeclampsia biomarker is higher than the reference level and if the level of the additional preeclampsia biomarker differs from the reference level for the additional preeclampsia biomarker.   
     
     
         67 . The method of  claim 1 , further comprising:
 assaying the biological sample to determine the level of an additional preeclampsia biomarker selected from the group consisting of PlGF, PP13, PAPP-A, Inhibin A, Activin A, MMP-9, Endothelin-1, P-selectin, NGAL, sEng, triglycerides, HDL cholesterol, LDL cholesterol, and combinations thereof.   
     
     
         68 . The method of  claim 1 , further comprising:
 diagnosing preeclampsia or HELLP syndrome if the level of the preeclampsia biomarker is higher than the reference level, and   if the preeclampsia biomarker is selected from the group consisting of PlGF, PP13, PAPP-A, HDL cholesterol, and combinations thereof, and the level of the preeclampsia biomarker is lower than the reference level, or   if the preeclampsia biomarker is selected from the group consisting of Inhibin A, Activin A, MMP-9, Endothelin-1, P-selectin, sEng, NGAL, triglycerides, LDL cholesterol and combinations thereof, and the level of the preeclampsia biomarker is higher than the reference level.   
     
     
         69 . A kit for diagnosing preeclampsia or HELLP syndrome in a subject in need thereof, comprising: one or more reagents comprising at least one detectably labeled probe for the detection of KIM-1, one or more complement proteins or components, or a combination thereof. 
     
     
         70 . An assay for diagnosing preeclampsia or HELLP syndrome, comprising:
 a solid phase;   a first reagent to react with a preeclampsia biomarker, wherein the first reagent is immobilized on the solid phase;   a second reagent to specifically react with a preeclampsia biomarker, wherein the second reagent comprise a label;   a substrate to react with the label; and   a third reagent to react with the second reagent to serve as a control.